Nanomedicine and nanotechnology-related publications made up 9% of all articles in 2022, according to Web of Science. This statistic underscores the ever-increasing importance of nanotechnology in advancing science and the significant contributions made by scientists worldwide. With China by far topping the list of countries with most nanotechnology publications (~100,000), followed by India and the United States as a close second/third (~25,000), Iran took a solid fourth place with a little over 10,000 papers. These numbers demonstrate the dedication and efforts by the people of Iran to use nanotechnology to advance science. The Iran Nanotechnology Innovation Council (INIC) was founded in 2003 (https://en.nano.ir/). The INIC's primary goal has been to guide Persian scientists to become one of the leading nations in nanotechnology (Ghazinoory et al., 2009). With this, Iran has elevated nanotechnology research and development to the level of a national strategic priority. In 2011, the Iranian Society of Nanomedicine (https://isnm.ir/en/) was established as a liaison between INIC and the “Iran Ministry of Health and Medical Education” to foster collaboration, knowledge exchange, and innovation within the national scientific community. It is worth noting that their remarkable progress has been achieved despite the significant challenges posed by international sanctions imposed on their country. Hence, we are pleased to introduce this special issue containing a collection of nine state-of-the art review articles from Iranian scientific leaders in the field of nanomedicine.

The first article provides an advanced review on magnetite-based “Janus” particles (Madadi & Khoee, 2023). Janus nanoparticles are structures with two or more terminal chemically distinct groups that face a different direction from the surface. These particles are named after the Roman god Janus, which is usually depicted as having two faces, with one looking to the future and one to the past. This asymmetry allows functionalization that is not possible with uniform particles having a single surface coating. Special emphasis is placed on their use as magnetically driven nanomotors and micromotors. Within the same entity, one part of the micromotor/nanomotor can act as an engine for self-propelled motion when activated, while the remaining particle serves as the functional material for various assigned functions, such as surveying sensors for the capture of specific analytes.

The preparation and stabilization of nanoemulsions is the next topic (Yousefpoor et al., 2023). Although many emulsified nanoformulations have been successfully developed, their production can be quite tricky. Miniscule amounts of contaminants, even in ultra-filtered, triple-distilled water, can interfere with the reproducibility of the final product. Similarly, scale-up for industrial production does not translate linearly in terms of the increased amounts of ingredients and reaction vessel volume. Preparation schemes vary from low-energy (phase-inversion, spontaneous assembly) to high-energy (high-pressure homogenization, sonication, microfluidization) methods. Minimal requirements for characterization are reviewed, with emphasis on drug release profiles. Safety and unwanted side effects, depending on the emulsion types, are also important parts of this advanced review.

Nanosized bioactive glasses are next (Kargozar et al., 2023), amorphous solids that belong to the bioceramics superfamily. The chemical structure of bioactive glasses provides an outstanding opportunity for adding a wide range of chemical elements (metallic or non-metallic) to their classical composition. They have been successfully used in various forms of cancer treatment strategies, including hyperthermia, photothermal therapy, brachytherapy, and anti-cancer drug delivery. The applications of these materials are still in their early stages, and the impact of their composition, biodegradation, size, and morphology on anticancer efficacy remains largely unexplored. This article also calls for standardized computational studies (in silico methods) to design the most effective glass formulations for cancer therapy approaches and to predict, to some extent, the relevant efficacy and therapeutic outcomes.

Plant virus-derived nanoparticles are a unique class of bionanomaterials with well-defined and uniform morphological homogeneity, ease of functionalization, biodegradability, water solubility, and high absorption efficiency. The fourth advanced review (Azizi et al., 2022) covers this emerging class of agents. Whether used for encapsulation of therapeutic or diagnostic agents inside their hollow cavity or surface modification of the capsid itself, they have recently been successfully used for targeted drug delivery, targeted gene therapy, cancer immunotherapy, photothermal and photodynamic therapy, and combinations thereof. As these are xenogeneic agents, immunogenicity has been of concern but paradoxically, this property could also be exploited for synergistic effects to activate immune cells (i.e., macrophages) when performing immunotherapy.

The fifth publication describes the use of polymeric nanofibers for controlled drug-release applications (Valizadeh et al., 2023). These (in)organic materials have large specific surface areas, high porosity, and excellent molecular alignment. Drug delivery can be made stimuli-responsive (i.e., dependent on redox potential, pH value, or enzyme expression) for endogenous triggered release or temperature- or light-dependent for exogenous induction. Other physical on-demand strategies include activation by focused ultrasound or electric and magnetic fields. Incorporating magnetic materials may also allow their use as implantable nanodevices for synergistic magnetic hyperthermia combined with chemotherapy when applying alternating current magnetic fields.

Review number six assesses the promises and pitfalls of translating gold nanoparticles into sensitizers for radiation therapy (Moloudi et al., 2023). In general, few clinical trial studies have yet been performed on drug delivery and photosensitization with lasers, and the nanoparticles still have a long way to go for clinical approval. This includes effective targeting and uptake by tumor cells when injected systemically, proper biodistribution throughout the entire tumor when injected locally (which would ensure eradication of all cells, including cancer stem cells), and eventual bioclearance from the body, especially when accumulation in normal, healthy tissue occurs. The results of seven clinical trials are discussed in detail. Despite the initial enthusiasm for these trials, the overall outcome has not lived up to expectations based on pre-clinical studies, with no trials performed yet beyond Phase I studies. Solutions for improvement of study designs are being offered to possibly change this future outlook.

The next topic is combined thermo- and chemo-radiotherapy of cancer (Shirvalilou et al., 2023). At first, (magnetic) hyperthermia was used as a standalone treatment, but more recently it is applied to support more conventional treatments such as chemotherapy and radiation therapy. Detailed accounts are provided for the (Arrhenius) relationship between heating and tumor cell kill, and how pH, hypoxia, and the cell cycle affect treatment efficacy. A particular topic of attention is the interplay between the three treatment modalities, for instance how hyperthermia can change tumor vascular permeability, drug uptake, and drug retention as a result of tissue pressure changes, enhancing chemotherapy in most cases. The central role of (magnetic) nanoparticles is discussed in view of the trimodal treatment approach.

Nanoscaffolds have been widely used in tissue engineering and regenerative medicine to provide a safe and natural environment for cellular repair. Various types of structures, including nanofibers, nanosheets, nanofilms, nanoclays, hollow spheres, and other nanoparticles are discussed in this penultimate review (Rahmani Del Bakhshayesh et al., 2023). Materials being discussed include carbon nanotube-based scaffolds, bioglass based (see also Kargozar et al., 2023), lipid based, graphene oxide based, boron nitride based, transition metal dichalcogenide based, and nanoclay based, to name a few. Special emphasis is placed on overall biocompatibility and toxicity, and the many available ways of making these scaffolds, notably by electro-spinning and bio-printing as the latest technologies.

This special issue ends with an emerging approach for stem cell therapy of neurological disorders, that is, delivering nanoparticle-labeled stem cells to the brain using the intranasal route, circumventing the blood–brain barrier (Alizadeh et al., 2023). By this means, stem cells can cross the nasal epithelium to the central nervous system either via the olfactory (nose) or respiratory (lung) epithelia. The advantage over intravenous administration or other delivery methods is a direct, targeted shot to the brain while avoiding first-pass metabolism in the body and undesired homing to other (filtering) normal tissues. Emphasis is placed on the use of neural stem cells and mesenchymal stem cells, as these have been clinically most widely used. Comparisons with other administration routes are made, largely based on in vivo magnetic resonance imaging studies of magnetically labeled cells, which can report on the spatiotemporal dynamics of cell distribution over time.

We hope you all will enjoy reading this special issue as much as we enjoyed putting it together.